Neuromodulators such as serotonin (5-HT) are often considered in the context of mood or appetite disorders, but they also strongly influence the way that auditory information is processed and perceived. However, we understand very little of how the actions of 5-HT on the neural circuitry of the auditory system are involved in normal perception or in disease. The proposed experiments will address these issues by examining the influence of two types of 5-HT receptor on frequency tuning of neurons in a midbrain auditory nucleus, the inferior colliculus (IC). Frequency tuning is a fundamental characteristic of auditory neurons, but can be changed by learning or by depriving the auditory system of its normal input. In previous studies of single neurons in the IC, one of the most prominent effects of 5-HT was on frequency tuning. Two 5-HT receptors, the 5-HT1A and 5-HT1B receptors, have opposing effects on tuning, with the 5-HT1A receptor limiting frequency tuning, and the 5-HT1B receptor expanding tuning. In pursuing this finding, the objectives of this proposal are 3-fold: 1) To more fully characterize how these two receptors change frequency tuning. This will be accomplished by using 2-tone stimuli to examine the interactions between the excitatory and inhibitory inputs that establish frequency tuning in the IC, while locally manipulating the receptors. 2) To test the hypothesis that the receptors act partly by affecting inhibitory inputs to IC neurons. This will be accomplished by determining whether blockers of inhibition also block the effects of the two receptors, and by determining whether activating the receptors alters directly visualized inhibitory inputs. 3) To establish whether these changes in frequency tuning occur in groups of neurons that play particular roles in the circuitry of the IC. This will be determined by identifying neurons morphologically by filling single neurons with neurobiotin and immunohistochemically by co-labeling neurons for the inhibitory neurotransmitter, GABA. The results of these studies will provide a rich functional profile of neuronal response properties and anatomy that will clarify the role of the 5-HT1A and 5-HT1B receptors in the IC and lay the groundwork for studying their role in auditory dysfunction. PUBLIC HEALTH RELEVANCE: The potential involvement of serotonin in auditory disorders that are primary or that are associated with affective disorders has received little attention. Defining how the 5-HT1A and 5-HT1B receptors act to alter frequency filtering in the IC will lay the groundwork for addressing the role of serotonin in auditory dysfunctions such as poor speech perception, auditory hypersensitivity, or tinnitus.